Aging is a multi-faceted process influenced by both genetic and environmental factors. Many pharmaceuticals and nutraceuticals have been shown to have prolongevity effects from studies in model organisms. Nutraceuticals made from various plants and fruits are rich in phytochemicals and possess diverse bioactivities, including anti-aging effects. However, the mechanisms underlying how dietary nutrients influence the prolongevity effects of interventions for promoting healthy aging are not well understood. Moreover, how and when the interventions with nutraceuticals or pharmaceuticals remain elusive. These issues are critical for developing effective interventions for promoting healthy aging in human. To this end, based on our previous findings that cranberry supplementation can significantly increase lifespan in Drosophila, we have investigated the mechanisms underlying the lifespan extension induced by cranberry supplementation and also the effect of calorie content influencing how cranberry supplementation promotes longevity in Drosophila. We have found that cranberry further extends lifespan of flies under dietary restriction, the latter of which is known to increase lifespan relative to diets with normal and rich calorie content. A manuscript is under preparation to describe these findings. This work provides a foundation for further investigating mechanistic studies on the effect of nutraceutical supplementation in delaying aging process and for designing cost effective and efficiency aging interventions in human. In our efforts to determine the general applicability of using cranberry as an effective aging intervention, we have investigated whether cranberry can promote longevity in other species. Through collaboration with Dr. Yuqing Dong at Clemson University, we have studied the prolongevity effect of cranberry and the underlying mechanisms in C. elegans and published a paper in AGE (2013) showing that cranberry can promote longevity likely through at least two pathways, insulin-like signaling and osmotic response pathways, in C. elegans. We have extended this line of research and investigated the effect of cranberry in alleviating symptoms of Alzheimers disease, a devastating aging-associated neurological disease. We have shown that cranberry supplementation can improve protein homeostasis and slow down the degeneration in a worm model of Alzheimers disease. This beneficial effect of cranberry is at least partially through HSF-1 pathway known to be involved in modulating lifespan and maintaining proteostasis. A manuscript describing these findings has been submitted and is under review in Journal of Gerontology Biological Sciences. This line of research together with our findings in Drosophila demonstrates the health benefits of cranberry supplementation in evolutionally divergent species. Many of the pathways critical for lifespan extension induced by cranberry, such as insulin-like pathways, are conserved among worms, flies and humans, suggesting that the likelihood of the similar beneficial effects of cranberry consumption in humans. These studies provide groundwork for developing effective interventions for promoting healthy aging in human using nature products, such as cranberry. In summary, we have investigated the prolongevity effects of a cranberry-containing nutraceutical in Drosophila and C. elegans. We have demonstrated the underlying mechanism of cranberry-induced lifespan extension and determined the optimal timing for inventions with cranberry. These findings provide the foundation for our future research directed towards understanding the molecular mechanisms underlying how nutraceuticals and pharmaceuticals promote and healthspan. These studies should provide valuable information for developing efficient interventions for promoting healthy aging in humans. This project should advance the objectives of the Translational Gerontology Branch and overall missions of the National Institute on Aging.